Fast effectiveness of a solubilized low-dose budesonide nasal spray in allergic rhinitis.

BACKGROUND: Budesonide, a poorly water-soluble corticosteroid, is currently marketed as a suspension. Budesolv is a novel aqueous formulation containing dissolved budesonide showing increased local availability in preclinical models. Budesolv contains ~85% less corticosteroid than the marketed comparator. OBJECTIVE: The study (EudraCT:2018-001324-19) was designed to assess non-inferiority of Budesolv compared to Rhinocort® Aqua 64 (RA) and early onset of action. METHODS: In a three-way cross-over double-blinded randomized trial, Budesolv 10 was compared to RA and placebo in grass pollen allergic rhinoconjunctivitis volunteers (n = 83 (ITT); n = 75 (PP)). On day 1, participants entered the Vienna Challenge Chamber (VCC) for 6 hours; first treatment took place at 1:45 hours after entry. Participants treated themselves for further 6 days; on day 8, the last treatment was applied before entering the VCC. Subjective symptom scores, nasal airflow and nasal secretion were measured regularly during allergen challenge. RESULTS: Budesolv 10 was equally effective compared to RA with respect to TNSS and nasal airflow after eight days of treatment with a strongly reduced dose (more than 80% reduction). After first dose, only Budesolv 10 showed a significant reduction of nasal and respiratory symptoms starting 90 minutes (P < .05) and 15 minutes (P < .05) after application onwards, respectively, demonstrating an early onset of efficacy. A clinically significant 1 point reduction in nasal symptom score was reached at 195 minutes (P < .05) after application. CONCLUSIONS AND CLINICAL RELEVANCE: The novel preservative-free, aqueous low-dose budesonide formulation is highly efficacious even after an initial single treatment. Thus, Budesolv 10 appears to be an effective acute treatment for allergic rhinitis as well as for AR comorbidities like mild asthma and conjunctivitis.

The surface microporosity of ceramic biomaterials influences the resorption capacity of osteoclasts.

This study investigated the influence of the surface microporosity of beta-tri-calcium phosphate (ß-TCP) ceramics on the resorption capacity of osteoclasts. This was achieved by first compacting commercially available ß-TCP powder into disks that were sintered at various temperatures, thereby yielding different surface microporosities. Scanning electron microscopy (SEM) and subsequent image processing verified different degrees of surface microporosity on the disks. Rabbit osteoclasts in a bone marrow derived cell suspension were then seeded onto these disks and incubated for 48 h. Tartrate resistant acid phosphatase (TRAP) staining confirmed the presence of osteoclasts on all disks. Actin ring staining that detected actively resorbing OCs showed an inverse linear correlation between the number of actively resorbing osteoclasts (percentage of total OCs on the surfaces) with surface microporosity. These findings should be taken into consideration for the design and/or production of new ß-TCP bone graft substitutes.

Fibrin-polyurethane composites for articular cartilage tissue engineering: a preliminary analysis.

In this study we investigated the use of a fibrin hydrogel to improve the potential of a polyurethane (PU) scaffold-based system for articular cartilage tissue engineering. PU-only ("no-fibrin") and PU-fibrin ("fibrin") composites were cultured for up to 28 days and analyzed for DNA content, glycosaminoglycan (GAG) content, type II collagen content, GAG release, and gene expression of aggrecan, collagen I, and collagen II. The use of fibrin allowed for higher viable cell-seeding efficiency (10% higher DNA content on day 2 in fibrin versus no-fibrin composites) and more even cell distribution on seeding, a more than 3-fold increase in the percentage of newly synthesized GAG retained in the constructs, and 2- to 6-fold higher levels of type II collagen and aggrecan gene expression through day 14. Addition of aprotinin to the medium inhibited fibrin degradation, most noticeably in the center of the constructs, but had little effect on biochemical composition or gene expression. Short-term mechanical compression (0-10% sinusoidal strain at 0.1 Hz for 1 h, applied twice daily for 3 days) doubled the rate of GAG release from the constructs, but had little effect on gene expression, regardless of the presence of fibrin. Although further work is needed to optimize this system, the addition of fibrin hydrogel to encapsulate cells in the stiff, macroporous PU scaffold is a step forward in our approach to articular cartilage tissue engineering.

A hydrogel system for stimulus-responsive, oxygen-sensitive in situ gelation.

A hydrogel system that is designed to gel due to oxidation by molecular oxygen is described. This is achieved by the use of a branched poly(ethylene glycol) modified with thiol end groups. A stable precursor molecule, starPEG thioacetate, was synthesized by radical addition of thioacetic acid to an intermediate starPEG allyl ether. Rapid deprotection of the thiol can be achieved using a base, e.g. sodium hydroxide, quantitatively liberating a thiol group and a non-toxic acetate ion. This step can be carried out under anaerobic conditions, yielding a solution with known thiol content that can be stored. The reaction with oxygen is accelerated by the use of a catalyst based on Fenton chemistry, which makes the material useful for biomedical applications where in situ polymerization of an injectable material is beneficial. This gelation takes place under near physiological conditions without the need for a cross-linking agent.